Composite materials using bone bioactive glass and ceramic fibers

ABSTRACT

Composite materials formed from bone bioactive glass or ceramic fibers and structural fibers are disclosed. In preferred embodiments, a braid or mesh of interwoven bone bioactive glass or ceramic fibers and structural fibers is impregnated with a polymeric material to provide a composite of suitable biocompatibility and structural integrity. Most preferably, the mesh or braid is designed so that the bioactive fibers are concentrated at the surface of the implant to create a surface comprised of at least 30% bioactive material, thereby providing enhanced bone ingrowth. The interweaving between the bone bioactive glass or ceramic fibers and the core of structural fibers overcomes the problems found in prior composite systems where the bioactive material delaminates from the polymer. Preferred bioactive materials include calcium phosphate ceramics and preferred structural fibers include carbon fibers. Further preferred bioactive materials include aluminum oxide at greater than 0.2%, by mole. Improved prosthetic implants and methods of affixing an implant are thus also disclosed.

This is a division of U.S. application Ser. No. 08/436,585, filed May 8,1995, pending, which is a continuation-in-part of U.S application Ser.No. 08/152,962, filed Nov. 15, 1993 issued as U.S. Pat. No. 5,468,544,Nov. 21, 1995.

The present invention relates to composites made from fibers comprisedof bioactive glass and the use of such composites to form implantablesurfaces. In particular, the present invention relates to compositescomprised of bone bioactive glass or ceramic fibers intermingled withstructural fibers such as carbon fibers in a matrix of a polymericmaterial.

BACKGROUND OF THE INVENTION

Low modulus composite materials have been employed as femoral componentsof hip implants to reduce stress shielding of the bone and consequentlyreduce bone tissue resorption. Currently, composite implants arestabilized in their bony bed by a press fit. With this method ofstabilization, however, optimum stress distribution effects are notfully realized.

Several attempts have been made to improve the fixation of compositefemoral implants to bone. These include porous polymer coatings andparticulate bioactive coatings. Implants using porous polymer coatingsseek to achieve fixation through mechanical interlocking between theimplant and surrounding bone tissue, while the bioactive coatings aredesigned to attain fixation through a chemical bond between the implantand bone.

Implant surfaces coated with polysulfone particles in an effort tocreate a porous coating which would behave similarly to a porous metalcoating are disclosed in M. Spector, et al., "Porous Polymers forBiological Fixation," Clin. Ortho. Rel. Res., 235:207-218 (1988).Although it is disclosed that some bone growth was evident, the majorityof the tissue about the implant surface was fibrous. The porous polymerdid not enhance the bone tissue growth in any way.

Composite system of calcium phosphate ceramic powder pressed onto apolymer surface and then cured are also known. See P. Boone, et al.,"Bone Attachment of HA Coated Polymers," J. Biomed. Mater. Res. 23, No.A2:183-199 (1989); and M. Zimmerman, et al., "The Attachment ofHydroxyapatite Coated Polysulfone to Bone," J. Appl. Biomat., 1:295-305(1990). These systems are provided in two fashions. First, the ceramicis flush with the polymer surface, hence, only bonding occurs. Second,the calcium phosphate particles extend from the polymer surface. Wheninterfacial bonding is tested, the failure is between the polymer andthe calcium phosphate particles. Hence, the interface between thecalcium phosphate particles and the polymer is the weak link in thesystem. These references disclose the use of polyurethane thermoset andpolysulfone thermoplastic polymers, a number of other polymers aresimilarly used as a matrix for a filler of calcium phosphate ceramicpowder in U.S. Pat. No. 4,202,055----Reiner et al. The ceramic particlesat the surface of this implant resorb and are replaced by bone tissue.There are no structural fibers and the polymer alone is intended to bearthe load. This limits the load-bearing applications of this material tothose of the polymer. An implantable bone fixation device comprised ofan absorbable polymer and a calcium phosphate ceramic powder fillermaterial is disclosed in U.S. Pat. No. 4,781,183----Casey et al. Thedevice disclosed is a temporary load bearing device which resorbs uponimplantation. The calcium phosphate particles are added for strength andalso resorb, therefore this device is not fixed to bone tissue throughthe chemical bonding of bioactive material or porous ingrowth.

Structural fibers will improve certain mechanical properties ofcomposite materials. For example, U.S. Pat. No. 4,239,113----Gross etal. discloses a composition of methylmethacrylate polymers and abioactive ceramic powder combined with vitreous mineral fibers less than20 millimeters long. This device is used as a grouting material to bondimplants to bone tissue. The chopped fibers are not specificallytailored or designed for mechanical property optimization. A similarcomposition is disclosed in U.S. Pat. No. 4,131,597----Bluethgen et al.,which mentions the use of glass or carbon fibers to add strength to thecomposite. This patent, however, does not specifically discuss placingfibers to achieve bone bonding regionally. Also, no method ofoptimization of material properties through arrangement of thestructural fibers is suggested. Finally, the method of fixation to beachieved by the disclosed material is not explained.

A similar approach using a textured device of carbon fiber/triazin,coated or non-coated with calcium phosphate particles is discussed in G.Maistrelli, et al., "Hydroxyapatite Coating on Carbon Composite HipImplants in Dogs," J. Bone Jt. Surg., 74-B:452-456 (1992). The resultsreported show a higher degree of bone contact for the coated devicesafter six months. However, longer studies are needed to evaluate thelong term fatigue effects on the triazin/calcium phosphate interface.

In all these prior art systems, however, it has been found that althougha bond between the substrate polymer and bone may be achieved throughthe use of a bioactive material at the interface, the resulting implantis still unsatisfactory. As discussed above, the significant limitationremains the interfacial bond between the bioactive material and thepolymer.

Much of the prior art discussed immediately above utilized calciumphosphate ceramic powders as the bioactive component of the composite.Bioactive glass materials were developed by Hench in 1969. See L. Hench,et al., "Bonding Mechanisms at the Interface of Ceramic ProstheticMaterials," J. Biomed. Mater. Res., 2:117-141 (1971). More recently,elongated, continuous bioactive glass fibers have been fabricated. SeeU. Pazzaglia, et al., "Study of the Osteoconductive Properties ofBioactive Glass Fibers," J. Biomed. Mater. Res., 23:1289-1297 (1989);and H. Tagai, et al., "Preparation of Apatite Glass Fiber forApplication as Biomaterials," Ceramics in Surgery, Vincenzini, P. (Ed.),Amsterdam, Elsevier Sci. Pub. Co. (1983), p. 387-393. The latterreference discloses bioactive glass fibers in resorbable bone plates.

As seen from the foregoing, it would be desirable to provide a compositematerial for use as a prosthetic device that could be designed toprovide a structural modulus that closely matched bone. It is thus anobject of the present invention to provide composite structures thatincorporate a bioactive material in a polymer matrix along with astructural fiber to provide adequate strength. Additionally, it is afurther object of the present invention to provide three dimensional andhybrid composite materials that overcome the deficiencies of the priorart, and in particular that provide an adequate interfacial bond betweenthe bioactive material and the polymer.

SUMMARY OF THE INVENTION

It has now been found that bone bioactive glass or ceramic fibers areuseful as a chemical bonding vehicle in combination with a structuralthree-dimensional braided fiber substrate. The bioactive fibers enhancebone growth and bond to surrounding bone tissue. These bone bioactiveglass or ceramic fibers are interwoven in the three dimensional braidwith carbon fibers and infiltrated with a thermoplastic polymer to forma three-dimensional bioactive composite material. The glass fibers arepreferably concentrated on the outer surface of the composite so as tobe exposed to physiological fluids upon implantation. This leaves thecarbon fibers concentrated in the center region of the implant materialto bear the majority of the load.

The stress transfer achieved by interfacial bonding between the implantand bone, combined with the "matched modulus" of the composite implant,provides near optimal stress distribution in the bone, thereby improvinglong term stability and fixation. In addition, with adequate fixation,there is decreased micromotion between the implant and bone, hence thepotential for abrasion of the composite material surface is greatlyreduced. Consequently, the chances of particulate debris from theimplant causing an inflammatory response, which often leads to loss ofimplant stability, are also greatly reduced.

BRIEF DESCRIPTION OF THE DRAWINGS

The file of this patent contains drawings executed in color. Copies ofthis patent with color drawings will be provided by the Patent andTrademark Office upon request and payment of the necessary fee.

FIG. 1 is an illustration of the apparatus used to draw bone bioactiveglass or ceramic fibers used in the present invention.

FIG. 2 is a photomicrograph of a section of bone showing ingrowthachieved in an implant.

FIG. 3 is a photomicrograph of a section of bone similar to FIG. 2, buttaken at higher magnification.

FIG. 4 is a cross-section of a composite fiber braid made in accordancewith the present invention.

FIG. 5 is a schematic illustrating the orientation and placement offibers in a textile woven from bone bioactive glass or ceramic fibersand structural fibers in accordance with the present invention.

FIG. 6 an elevation view of a hip prosthesis made in accordance with thepresent invention.

FIG. 7 depicts the elemental concentration on the glass fiber surfaceafter immersion in simulated body fluid versus time.

FIG. 8 depicts the interfacial bond strength of a composite implant anda polymer implant at three weeks and six weeks implantation time.

FIG. 9 is a photomicrograph of the composite implant/bone interfaceafter six weeks implantation, 200× magnification.

FIG. 10 is a photomicrograph of the composite implant/bone interfaceafter three weeks implantation, 200× magnification.

FIG. 11 is a scanning electron micrograph of the composite implant/boneinterface after six weeks implantation.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The uniquely constructed composite material of the present invention isable to maintain continuity from the interface of the structuralsubstrate and the carbon fiber/polymer interface, and to the interfacebetween the bioactive surface and the bioactive glass fiber/polymerinterface. As explained below, the bioactive section of the implantmaterial is integrally incorporated into the substrate through a braidedinterface. Because of this construction there is an increased bondsurface between the bioactive material and the polymer that imparts ahigher degree of integrity to the bioactive composite material ascompared to a particulate coating on the surface of a polymericcomposite, such as that found in the prior art. Thus, the likelihood ofdelamination of the bioactive material from the polymer is greatlyreduced. Thus, the present invention provides interfacial bondingbetween the polymer and bioactive coating, overcoming the mainlimitation of the prior art.

The configuration of the fiber architecture results in the load beingapplied to a central portion of the composite, which is preferablycomprised of strong, inert fibers such as carbon fibers or otherbiocompatible fibers integrated with the bioactive fiber surface. Stressis therefore transferred from the inert structural fibers to thebioactive fibers at the implant surface. The integration also serves toincrease the mechanical integrity of the material system and preventdelamination within the composite structure.

In the local environment of the bioactive glass fiber, a partialdegradation occurs. As the bioactive glass fiber is resorbed it isreplaced by bone tissue; the bone tissue is chemically bonded to theglass fiber and also interlocked with these fibers. Furthermore, thebioactivity reactions occurring at the glass surface lead to aprecipitation layer on the polymer. This layer, in turn, promotes bonetissue formation and bonding. The triple means of interfacial bondingleads to an interface which stabilizes the implant in its bony bed andprovides stress transfer from the implant across the bonded interfaceinto bone tissue. The bone is stressed, thus limiting bone tissueresorption due to stress shielding. This significant occurrence willincrease the life of an implant because fixation and stability will notbe lost due to bone tissue resorption, which is an initiator in thecascade of events leading to prosthesis loosening.

In the present invention, a composition of bone bioactive glass orceramic fibers is preferred. In the case of glass the preferredcomposition leads to a slowly reacting glass while maintaining theability to be fabricated. A slow reaction rate is desired because alarge surface area of glass is exposed to physiological solutions duringimplantation with glass in a fibrous configuration. A bioactive glassthat quickly degrades may lead to an adverse inflammatory response,impeding bone growth and bonding. The tradeoff is that since the glassmust be drawn into continuous fibers it cannot be too viscous or toofluid, or the fibers would break upon drawing. Describing thecompositional range for materials capable of being drawn into bioactiveglass or ceramic fibers thus involves bioactivity versusmanufacturability. A most preferred composition that can be successfullydrawn into fibers while maintaining bioactivity is: 52% SiO₂ ; 30% Na₂O; 15% CaO; 3% P₂ O₅. In developing this range, experimental trialsshowed that a composition of 52% SiO₂ ; 32% Cao; 3% P₂ O₅ ; 13% Na₂ O;would be bioactive, however, it is difficult to draw this composition ofglass into fibers. This is because the CaO and the P₂ O₅ work againstfiberization, while the Na₂ O and SiO₂ work for it. It was also foundthat a composition of 52% SiO₂ ; 27% CaO; 2% P₂ O₅ ; 19% Na₂ O led tothe same difficulties relating to fiberization. The following trendswere seen among experimental batches:

    ______________________________________                                                Fiberization                                                                             Bioactivity                                                ______________________________________                                        SiO.sub.2 increases    40-60% give bioactivity,                                                      decreased bioactivity                                                         with higher SiO.sub.2                                  CaO       decreases    increases                                              P.sub.2 O.sub.5                                                                         decreases    increases, but not                                                            required to                                                                   achieve bioactivity                                    Na.sub.2 O                                                                              increases    decreases                                              ______________________________________                                    

Thus, in preferred embodiments, glass compositions used with the presentinvention will be comprised of 40-60% SiO₂ ; 10-21% CaO; 0-4% P₂ O₅ ;and 19-30% NaO. A more preferred range will be comprised of 45-55% SiO₂15-20% CaO; 25-35% Na₂ O; and 0-3% P₂ O₅ by mole. As noted above, themost preferred composition on the criteria of slow reaction rate and theability to be manufactured is 52% SiO₂ ; 30% Na₂ O; 15% CaO; 3% P₂ O₅ bymole. Modifiers which may be added to the base composition (by mole)include: 0-3% K₂ O; 0-2% MgO; 0-1% Al₂ O₃ ; and 0-3% F₂. Preferably, Al₂O₃ is added in an amount greater than 0.2%. As known in the art, suchmodifiers may be added in small quantities to vary the properties andprocess parameters and further improve the control of bioactivity andmanufacturability.

The following Examples will discuss and explain the formation of acontinuous fiber of a bioactive glass for use in a braided fiber and awoven fabric, both of which are impregnated with a polymeric materialsuch as polysulfone to create a three dimensional composite material.

EXAMPLE I

The most preferred glass fiber composition disclosed immediately above(52% SiO₂, 30% Na₂ O, 15% CaO, and 3% P₂ O₅ (in mole %)) was preparedfrom powders. The powders were weighed, mixed, and melted at 1350° C.for two hours in a silica crucible. The glass drawing apparatus used forthis Example is shown in FIG. 1 and includes a resistance heatedplatinum crucible 50 with an orifice at the bottom. Glass shards wereplaced into the crucible 50 and melted at approximately 1150° C. Theviscous melt formed a meniscus at the crucible orifice 52. To form thefiber 100, the glass meniscus was gently touched with a glass rod andthe glass rod was quickly, yet smoothly, pulled from the crucibleorifice 52 to form a glass fiber 100 from the melt. The fiber 100 wasmanually pulled and attached to the take-up wheel 60 spinning at 300-500rpm, as determined by the speed control 72 attached tot he motor 70 thatrotates the take-up wheel 60. A smooth, continuous glass fiber 10-13microns in diameter was obtained.

Polymer plates were manufactured using a closed die and a hot press. Thepolymer (polysulfone) was weighed and dried in an oven at 163° C. fortwo hours to drive out excess moisture. The mold was cleaned withethanol and sprayed with teflon mold release. The thermoplastic powderwas poured into the mold and the mold was placed in the hot press. Thepress was heated to 260° C. and pressure was then applied to 14,000 lbsand released. This was repeated twice. The mold was then heated to 300°C. and a pressure of 620 psi was maintained for thirty minutes. At thistime the pressure was released and the mold was air cooled.

The same processing parameters were followed to make plates of acomposite material. The polymer was first mixed with chopped glassfibers and then processed with the closed die in the hot press, asdescribed above.

Plugs 4 mm in diameter and 3 mm thick, were machined out of both thepolymer plates and the plates that included the chopped bioactive fibersusing a core drill tip. The samples were then cleaned with soap andwater to remove cutting fluids, and ultrasonically cleaned in ethanoland deionized water, being dried after each cleaning. The implants weresterilized with ethylene oxide.

One bioactive glass fiber/polysulfone and one control polysulfone plugwere implanted bilaterally in the medial proximal aspect of the tibiausing aseptic techniques. Each rabbit served as its own control. Fiverabbits were euthanized at three weeks and five at six weeks.

The retrieved tibiae were immersed in formalin fixative for two weeks.They were rinsed in deionized water and gross sectioned with a low speedblade saw using 70% ethanol as cutting fluid. The sections weredehydrated according to a graded alcohol immersion plan from 70% ethanolto 100% absolute ethanol over a two week period. Following dehydration,the specimens were sectioned perpendicular to the implant long axis intoapproximately 1 mm thick sections. The sections were infiltrated withSpurr's embedding media according to a graded infiltration sequence in avacuum desiccator using polyethylene embedding molds. The Spurr'sinfiltration cycle was as follows:

    ______________________________________                                         25% Spurr's*/75% ethanol                                                                         2 days (change day 2)                                      50% Spurr's*/50% ethanol                                                                         2 days (change day 2)                                      75% Spurr's*/25% ethanol                                                                         2 days                                                    100% Spurr's*       1 day                                                     100% Spurr's (.04 DMAE)                                                                           1 day                                                     ______________________________________                                         *No DMAE (n,ndimethylaminoethanol) added                                 

The specimens were then cured for 2 days in an oven at 21° C. Followingembedding, the specimens were sectioned to approximately 0.5 mm thicksections using a low speed diamond wafered rotating blade saw. Thesesections were ground and polished using 800 and 1200 grit paper to afinal section thickness of about 50 μm. The sections were stained usingVillanueva Mineralized bone Stain (Polyscientific, New York).

As seen in FIG. 2, taken at 400×. The composite material shows veryclose apposition to bone in areas of high fiber concentration. In theseareas, bone bioactive glass or ceramic fibers are partially resorbed,more clearly seen in FIG. 3, taken at 1000×. In addition, in regionswhere fibers are close together and bone apposition is achieved, thereis also bone apposition to the adjacent polysulfone matrix. In contrast,the polysulfone implants show bone tissue surrounding the plug, but withan interposing layer between the implant and bone tissue.

Thus, the foregoing Example shows that the bioactive glassfiber/polysulfone plugs made in accordance with the present inventionachieve a bond between surrounding bone tissue and the glass fibers atthe implant surface. The bonded fibers are partially resorbed with bonetissue replacing the glass. Consequently, the method of glass fiberfixation to bone is not only by chemical bonding, but also bymicromechanical interlocking. Additionally, there appears to be a bondbetween the adjacent polymer and surrounding bone tissue. This wouldlead to increased areas of fixation between the composite and bonebeyond that of the fiber itself.

The bond between polysulfone and bone may be due to a calcium phosphatelayer being precipitated onto the adjacent polymer surface as it wasbeing precipitated onto the glass fiber. Once this calcium phosphatelayer is formed, the polymer itself may act as a substrate for bonegrowth. Similar findings after implantation of a titaniumfiber/bioactive glass composite in dogs were recently reported. Van Hoveet al., Bioceramics Vol. 6, P. Ducheyne and D. Christiansen, eds., pp.319-325, Butterworth-Heinemann, Oxford (1993). This study shows bonegrowth over a titanium fiber which was between two islands of bioactiveglass. If the separation between the glass was less than 50 microns, thetitanium was covered with bone, but if it was greater than 100 microns(two fiber diameters) there was incomplete bone coverage. An in vitrostudy has concluded that when a polymer is faced 1 mm or less away froma bioactive glass in simulated body fluid, a calcium phosphate layer isprecipitated onto the polymer surface. See T. Kokubo, et al,"International Symposium on Ceramics in Medicine," Butterworth-HeinemannLtd., London (1991).

The histological observations of the foregoing Example indicate thatbone bioactive glass or ceramic fibers in combination with polysulfonepolymer will bond to bone tissue. This finding indicates that bonebioactive glass or ceramic fibers on the surface region of low moduluscomposite implants, such as hip stems and bone plates will achieveimproved results.

Another aspect of the present invention is the optimization of theamount of fiber used in the composite. As explained above, previousbioactive polymeric composites had used continuous particle coatings onthe surface of polymers or polymeric composites with a bioactive powderdispersed through the polymer matrix. It has been determined havingsurface area partially covered by bioactive glass in a composite formleads to bone bonding in vivo. A calcium phosphate layer is thesubstrate for bone growth. As explained above, the desirable developmentof a calcium phosphate layer on a non-bioactive material is possible ifthe material is in close apposition to the bioactive glass.Consequently, it has been found that a composite with only a partialbioactive surface would still achieve bonding. Preferably, theproportion of bioactive surface area exposed should be greater than 30%of the total surface area and the bioactive material should behomogeneously distributed over the surface of the composite to maintainthe 30% surface area of bioactive material over the entire surfacedesired for fixation.

Based upon the foregoing, it has also been discovered that fibers madein accordance with Example I and similar fibers can be advantageouslyused in composite materials that incorporate a structural fiber alongwith the polymer and the bioactive fiber. Thus, the present inventionalso relates to composite materials formed of woven, intermingled orjuxtaposed elongated fibers of both a bioactive material and anothermaterial chosen for its structural properties. These two fibers arecombined in a polymeric matrix. The following Examples will illustrateembodiments of this aspect of the present invention.

EXAMPLE II

One manner by which the location and density of fibers within acomposite can be controlled is by forming a braid of one or more typesof fibers and impregnating the braid with a filler material, such as apolymer. In preferred embodiments of the present invention, continuousbone bioactive glass or ceramic fibers are grouped into 5000 filamentfiber bundles. The fiber bundles (or "tow") are interwoven with carbonfibers into a braided textile preform. Most preferably, the bonebioactive glass or ceramic fibers are made in accordance with thecomposition formulation set forth above. As seen in FIG. 4, a preferredconstruction has glass fibers 100 woven into a three dimensional tubeabout a central, but separate, carbon fiber core 110. The two braids arewoven simultaneously while the carbon fibers in the core 110 and glassfibers 100 at the carbon/glass interface are interwoven, overlaid orotherwise intermingled. This results in structural interlocking andbrings continuity to the structure, even before the polymer isinfiltrated.

To create a composite in accordance with this embodiment of theinvention, the carbon fibers in the core 110 are commingled with polymerand unidirectional thick polymer fibers are intermingled with the glassfibers 100 in the outer region of the preform. The hybrid preform isthen processed in a closed die using a hot press, as described above.The amount of polymer is calculated to give the final total volumefraction desired, thus no additional polymer is added before processing.Also, the resulting composite does not need to be injection molded dueto the placement of the polymer fibers so as to achieve uniform polymerdistribution throughout the fibrous preform. The final composite ismachined to expose bioactive glass 100 fibers at the surface.

The present invention is also directed to the integration of a bioactivephase in fibrous form into a carbon fiber, three dimensional structuralreinforcement network. This results in a delamination resistant,interpenetrating fibrous network which allows bone tissue ingrowth.

EXAMPLE III

To facilitate composite processing, a thermoplastic matrix infilamentous form is co-mingled with the reinforcement fibers. As aresult, the thermoplastic fibers are uniformly distributed through outthe structure. A composite can be formed with bioactive fibers and bythe application of heat and pressure to melt the thermoplastic accordingto well-established regimens known in the art.

By proper selection of fiber architecture and textile processingtechnique, the quantity and distribution of the bioactive phase can becontrolled so that a preferred concentration of the bioactive fibers itdisposed near the surface of the structure. The thermal and mechanicalproperties of the composite system can be further tailored by changingthe fiber volume fraction and fiber orientation distribution. Dependingon the type of implant, two or three dimensional fiber architectures canbe selected and fabricated into net shape or near-net shape fibrousassemblies by weaving, knitting or braiding techniques, such as thosedisclosed in F. K. Ko, "Preform Fiber Architecture for Ceramic MatrixComposites," Bull. Am. Cer. Soc. (February 1989).

For illustrational purposes, a three dimensional hybrid mesh will beprovided as a specific example. It should be noted, however, that thesame principles can be applied to cylindrical shapes and other complexstructural shapes as seen in the three dimensional braiding loom designdiagram illustrated in FIG. 5.

In FIG. 5, the X's represent the bone bioactive glass or ceramic fibers,the number and distribution of which can vary, and the O's are astructural fiber, preferably carbon fibers, which also may be providedin large and small bundles. The vertical rows of the loom are called"tracks" whereas the horizontal rows of the loom are "columns." As knownin the art, a three dimensional braided structure is fabricated on thealternate motions of tracks and columns of bundles of fibers attached toa carrier based on the movement instructions indicated in the track andcolumn direction in an alternate manner. An "0" means no movement, and a"1" means moving in the positive direction by one carrier position and a"-1" means moving the carrier in the opposite direction of the otherhalf of the carrier in the same direction. Naturally, a "2" means movingtwo carrier positions.

In a preferred embodiment, the integration of the bone bioactive glassor ceramic fibers into the carbon fiber in an interfacial region isaccommodate by the position of the carrier in track/column coordinates6/6, 6/7; 7/7, 7/8; 8/6, 8/7; 9/7, 9/8; 10/6, 10/7; 11/7, 11/8; 12/6,12/7; 13/7, 13/8 being exchanged after each cycle of track/columnmovement.

From the foregoing, it can be seen that for a given yarn bundle size,the fiber orientation and fiber volume fraction can be designed. Knowingthe fiber and matrix material properties, the elastic properties in theform of a stiffness matrix can be established for the composite. Finiteelement analysis can also be performed to assess the stress-strainresponse of the implant under a set of boundary conditions. This preformdesign, micromechanics analysis and structural mechanics analysis can beperformed in an iterative manner to optimize the design of the implantand predict the performance capability of the structure.

Additional aspects of the present invention will best be understood withreference to FIG. 6, which illustrates a hip implant prosthesis 200 asan example of a composite structure that can be constructed using thepresent invention. First, it will be understood by those of skill in theart that the surface, or part of the surface of the prosthesis 200 canbe covered with grooves 210 or other surface irregularities. Forexample, as seen in FIG. 6, it is preferred that the proximalcircumferential third of the prosthesis 220 have grooves. These featuresaid in the macroscopic aspects of bone fixation and have been shown tobe beneficial. In accordance with the present invention, the grooves 210are most preferably formed by molding the preform to the desiredtexture, rather than machining a smooth surface.

Additionally, the present invention also permits bioactive andstructural fibers to be localized to achieve a local fixation using abioactive surface. In other words, the fibers can be varied so that thebioactivity is concentrated at a particular section or portion of animplant, device or prosthesis. Referring still to FIG. 6, the hipprosthesis 200 would most preferably have the bioactive fibersconcentrated in the proximal one third 220 of the implant device. It hasbeen shown that proximal stress transfer in a total hip arthroplasty isbetter achieved by using a material with fixation to bone in thisregion.

Thus, it will be appreciated that the present invention is veryversatile in many of its parameters. The bone bioactive glass or ceramicfiber can be selected from bioactive glass or glass-ceramic materials,including calcium phosphate ceramic fibers. The polymer system used maybe any polymer which bonds to the bone bioactive glass or ceramicfibers, is biocompatible, and does not inhibit the bioactivity of thefibers in vivo. Examples of such polymer systems are polysulfone,polyetheretherketone (PEEK), and polyetherketoneketone (PEKK). Thestructural fiber can be any inert fiber that fits the constraints ofbiocompatibility and exhibits the ability to bond to the chosen polymer.In addition to the carbon fibers disclosed above, such fibers includeinert high strength glass, aramid fibers, and inert ceramic fibers, suchas alumina. The fiber orientation and type of weave may be varied fordifferent applications and can be pre-selected and optimized using wellknown analysis techniques. Moreover, the disclosed hybrid wovenbioactive composite can be constructed not only as the three dimensionalbraided textile structure discussed above, but any woven textilestructure such as a two-dimensional braid, fiber interlock weave, orlaminated composite, among others. Finally, those of skill in the artwill understand that the present invention may be adapted to manyapplications where material shape, strength, stiffness, and fixation tobone are among the design parameters. In accordance with the presentinvention fibrous composites of biocompatible materials can be made intobioactive composites by incorporating bone bioactive glass or ceramicfibers into the weave at the bone contact surface.

EXAMPLE IV

Glass fibers having a molar composition of 52% SiO₂, 15% CaO, 3% P₂ O₅,and 30% Na₂ O were supplied by Glass Incorporated International, Covina,Calif., USA. The glass fibers were weighed and immersed in a simulatedblood plasma solution (SBF) which consisted oftrishydroxymethylaminomethane complimented with the following ions: 152mM Na⁺, 135 mM Cl²⁺, 5 mM K⁺, 2.5 mM Ca⁺², 1.5 mM Mg⁺², 27 mM HCO₃ ⁻,0.5 mM SO₄ ⁻, and 1.0 mM H₂ PO₄ ⁻, at the following time periods: 1, 3,and 8 hours and 1, 3, and 10 days. Using an average glass fiber diameterof 15 microns, the fiber surface area to solution volume ratio wasselected as 0.08 cm⁻¹, which led to a post immersion pH in thephysiological range.

The samples were immersed in closed vials on a shaker table moving at200 rev/min in an incubator at 37° C. Upon removal from solution thefibers were rinsed in acetone and dried in an oven at 37° C.

The reacted fibers were characterized using scanning electron microscopywith energy-dispersive X-ray analysis (SEM/EDXA). For SEM/EDXA, thefibers were mounted on an aluminum stub with silver paint and ionsputter coated with carbon to enhance conductivity. The analysis wasperformed at 15kV on a Joel JSM-T330A scanning microscope, Peabody,Mass., USA, with a KEVEX surface analysis system, Fisons Instruments,San Carlos, Calif.

The SEM and EDXA results were obtained for the surface of unimmersedglass fibers and the six immersion times: 1, 3, and 8 hours, 1, 3, and10 days. In the first three hours of immersion in SBF there was adecrease in the sodium peak, while the glass fiber surface showedlimited change in morphology.

A reduction in sodium on the surface of the glass was identified in thefirst eight hours, using EDXA. After one day of immersion in SBF, thecalcium and phosphorous peaks were greatly reduced and the silicon peakshowed high intensity, as determined by EDXA. Uniformly dispersedsnowflake-like formations were dispersed over the surface of the fibers.These regions measured approximately 5 microns in diameter and appearedflat against the surface of the glass fiber. The snowflake-likeformations had strong silicon peaks, but also showed the presence ofcalcium and phosphorous, as well as smaller amounts of sodium andchlorine.

After three days of immersion in SBF, per EDXA, the silicon peak wasmuch less intense, while the calcium and phosphorous peaks were strong.Here the ratio of calcium to phosphorous was 1.2. The surface of theglass fiber had non-homogeneously dispersed nodules which ranged from1-4 microns in diameter. The larger nodules seemed to be a combinationof smaller ones which had agglomerated. These nodules were not flushwith the fiber surface. The underlying areas of the fiber, without largenodules showed a more mottled surface which was fairly homogeneous.

After a ten day immersion period, the silicon peak was absent from thesurface scan, which indicated the presence of only calcium andphosphorous, as determined by EDXA. The calcium to phosphorous ratio was1.4. The morphology of the fiber surface was much like that after threedays immersion, although even larger nodules and a more textured surfacewas present. The nodules had grown to approximately 5 microns indiameter.

The elemental concentrations of silica, calcium, phosphorous, andsodium, as measured by EDXA, versus immersion time are depictedgraphically in FIG. 7.

Classification of the in vitro reaction stages of the bioactive glassfibers according to the Hench system puts stages 1-3 in the first eighthours to 1 day. Stage 4corresponds to 3 days immersion and Stage 5 is at10 days immersion. A significant difference between 45S5 bioactive glassresults and our own glass fibers is in the time differential. By 8 hoursimmersion, 45S5 bioactive glass had completed Stage 4 and was beginningStage 5, which plateaus out to eleven days. In the bioactive glassfibers, Stage 5or the formation of crystalline calcium phosphate did notoccur at 3 days but was present at 10 days. Therefore, the bioactiveglass fibers exhibited a reduced rate of surface reactivity, whencompared to 45S5 bioactive glass.

While a slower rate of reactivity could be explained by crystallinity inthe glass, our glass fibers were determined to be amorphous. A morelikely explanation of the reduced rate of reactivity is related to theglass composition. Al₂ O₃ was shown to be present in the glass by X-rayfluorescence and chemical analysis in a quantity greater than previouslyincorporated, and less than 1% by weight.

The Covina fibers were analyzed using X-ray fluorescence to identify anycontaminants within the glass fibers. The chemical composition of theCovina fibers was verified using standard glass chemical analysistechniques. For chemical analysis, the glass was attacked with a mixtureof hydrofluoric and perchloric acids. After evaporation, the residue wasdissolved with nitric acid and diluted to 250 mL. The elements wereanalyzed by atomic absorption spectroscopy, colorimetry and gravimetry.These analyses were performed by Institut National du Verre, Charleroi,Belgium.

X-ray diffraction (XRD) measurements using the Covina fibers were takenas 2θ varied from 10-150 using an automatic Rigaku diffractometer withCu Kα . Data collection was performed with a receiving slit of 0.15 mm,a 2 scanspeed of 1/min and a 2 scanstep of 0.02. Only non-immersedfibers were evaluated to determine the degree of crystallinity of theglass fibers.

XRD showed a low broad peak representing an amorphous material andseveral sharper peaks. The sharper peaks corresponded to those ofaluminum which came from the sample holder. The as-drawn fibers weretherefore amorphous. Because the gel layer is the weakest portion of thebond, a reduction of the silica layer thickness would seem to result inincreased interfacial bond strength.

X-ray fluorescence was used to determine the relative amounts ofcompounds present in the glass fibers. The results are presented inTable I. Precise compositional concentrations could not be obtainedusing this method for our glass because no prior standards have beendeveloped for this unique glass composition. The main elements werefound in the proportions shown, as were smaller quantities of otherelements, including modifiers. Most modifiers were determined to bepresent in amounts previously used in the art. Surprisingly, however,the modifier Al₂ O₃ was determined to be present in an amount greaterthan previously used ----0.95%.

                  TABLE I                                                         ______________________________________                                               Oxide         Weight %                                                 ______________________________________                                               SiO2          53%                                                             Al2O3         0.95%                                                           Na2O          28.9%                                                           K2O           0.05%                                                           CaO           15.8%                                                           MgO           1.42%                                                           Fe2O3         0.10%                                                           TiO2          0.05%                                                           P2O5          5.9%                                                            SO3, ZrO2     trace                                                    ______________________________________                                    

Chemical analysis using atomic absorption spectroscopy, colorimetry, andgravimetry are more quantitative in the absence of a previouslydeveloped standard than X-ray fluorescence. The results for thischemical analysis are shown in Table II in weight percentages. Again,Al₂ O₃ was found to be present at an amount greater than previously used----0.65%.

                  TABLE II                                                        ______________________________________                                               Oxide Weight %                                                         ______________________________________                                               SiO.sub.2                                                                           50.63                                                                   Al.sub.2 O.sub.3                                                                    0.653                                                                   Na.sub.2 O                                                                          26.80                                                                   K.sub.2 O                                                                           0.020                                                                   CaO   13.90                                                                   MgO   1.379                                                                   Fe.sub.2 O.sub.3                                                                    0.062                                                                   TiO.sub.2                                                                           0.008                                                                   P.sub.2 O.sub.5                                                                     6.30                                                                    SO.sub.3                                                                            0.041                                                                   ZrO.sub.2                                                                           0.013                                                            ______________________________________                                    

The addition of the multivalent cation (Al⁺³) to the glass compositionhas been previously shown to greatly reduce the rate of bioactivity(Gross et al., CRC Critical Reviews in Biocompatibility, 4:2 (1988);Hench, L. L., Handbook of Bioactive Ceramics, Vol. I, T. Yamamuro, L. L.Hench, and J. Wilson, eds., pp. 7-23, CRC Press, Boca Raton (1990);Kokubo et al., High Tech Ceramics, P. Vincenzini, ed., pp. 175-184 ,Elsevier, B. V., Amsterdam (1987); Kokubo et al., Materials in Medicine,3:79-83 (1992); and Kokubo et al., Proceedings of XV InternationalCongress of Glass, Vol. 3a, O. V. Mazurin, ed., pp. 114-119, Leningrad(1988)) primarily due to the increased network forming of the oxide. Ithas been hypothesized that alumina can tie up hydrated silica gel whichresults in limited or inhibited calcium and phosphorous formation withinthe gel layer (Gross et al., 1988, supra). Further, Al⁺³ ions mayprecipitate onto the surface and form carbonates, oxides, or hydroxides(Hench, L. L., 1990, supra), also preventing the incorporation ofcalcium and phosphorous in the gel.

The foregoing results indicate that the greater Al₂ O₃ content has,surprisingly, counteracted the effect of Na₂ O on rate of surfacereactivity in the present fiber composition. As is disclosed below, thisimproved performance of the fibers in vivo.

EXAMPLE V

Composites as described in Example IV and all-polymer control specimenswere implanted in the femoral cortex of eighteen rabbits. Eight rabbitswere euthanized at three weeks and ten at six weeks. The retrievedsections of implant and bone were evaluated mechanically to quantify theinterfacial bond strength; histologically, to observe the bonetissue/biomaterial interactions; and histomorphometrically, to quantifythe amount of bone tissue present at the implant surface.

Both the polymer and the composite plates were fabricated using the samemethods as described above. The composites contained approximately 30%by volume of glass fibers. The plates were machined into 3mm (0.125 in.)diameter and 15 mm (0.6 in) length implants. The surface roughness ofthe implants was determined using an optical profiler (Wyco, Tuscon,Ariz.).

One composite and one control polysulfone specimen were implantedbilaterally in the distal femur using aseptic techniques. The animalswere anesthetized, shaved and prepped with betadine solution. The skinwas incised, muscle layers were separated, and the periosteum waselevated away from the bone surface. A scalpel was used to mark thelocation of the implantation site and then a hand-powered drill withburr was used to create the transcortical cylindrical defect into whichthe plug was press-fit. Closure was in two stages: continuous suturesclosure of the periosteum and soft tissue and continuous subcutaneousclosure of the skin. The wounds were dressed and antibiotics wereadministered three days post-operatively. Radiographs were taken withinone week after surgery. Eight rabbits were euthanized at three weeks andten at six weeks.

After euthanasia by injection of nembutal, each femur was harvested. Thebones were gross sectioned in the region of the implant using saline asa cutting fluid while maintaining moisture in the samples. Theimplant/bone composite was then sectioned transverse to the long axis ofthe implant, leaving half of the implant/bone section for mechanicaltest and the remaining half for histology. The mechanical test specimenwas then stabilized in the test fixture using an acrylic polymer withthe long axis of the implant perpendicular to the flat bottom of thefixture. Still keeping the sample moist, the assembly was placed in amanner to align the specimen long axis with the load direction.

Testing was performed on an Instron mechanical test machine (Model 1321)using a cross-head speed of 5 mm/min (0.2 in/min). Load and cross-headdisplacement data were recorded on a personal computer using LabtechNotebook (Laboratory Technologies Corporation) software at a samplingrate of 10 measurements/sec.

Of the thirty-six femora which were implanted with either a composite orpolymer biomaterial, thirty-four were mechanically tested. A three weekfemur was fractured and the implant was removed from the mechanical testexperiment; a six week polymer implant was not included in the databecause the implantation site was too close to the femoral condyles.

Interfacial bond strength values are shown in FIG. 8. The mean shearstrength between the bioactive glass fiber/polymer composite and bonetissue after six weeks was 12.4 MPa (1798 psi), compared to the controlpolymer which had a mean value of 5.2 MPa (358 psi). Interfacial bondstrengths for the polymer at the two time points did not changesignificantly.

After retrieval, the untested bone/implant samples were dehyrated in asolution of one part formaldehyde, neutralized with CaCO₃ (50 g/L) andtwo parts 80% ethanol for a minimum of 24 hours. Following fixation, theblocks of tissue were consecutively dehydrated for 24 hours in each 70%,80%, 90%, and 94% ethanol and for 48 hours in absolute ethanol. Thesamples were then embedded in methylmethacrylate by immersing in puremethylmethacrylate for six days and then in a mixture ofmethylmethacrylate with benzoylperoxide and plastoid N for three days.The samples were cured in an oven at 60° C.

Embedded samples were sectioned and ground with a final polish using 600grid SiC paper. Half of the sections were stained with Stevenel's blueand Van Gieson's picrofuchsin. Stained sections were examined using thelight microscope and unstained sections were sputter coated with carbonand analyzed using SEM/EDXA.

The histological sections were quantitatively analyzed by measuring bonecontact at implant surface as a percentage of linear area. Themeasurements from the various sections for each specimen were averagedto obtain one data point per specimen. The bone contact measurementsbetween the polymer and composite at both time points were comparedusing two-way analysis of variance with replication and the pairwisecomparisons were analyzed using a t-test with Bonferroni adjustment(Systat, Systat, Inc.). Within the six week data set, a regressionanalysis was performed to determine the relationship between bonecontact area and interfacial bond strength for both the polymer andcomposite implants.

The composite material showed very close apposition to bone tissue atboth three and six weeks. As seen in FIG. 9, by six weeks the bonetissue was well-integrated with the composite material. The bone wasdirectly opposed to both fibers and polymer. The same observation wasdetected in FIG. 10 where the bone tissue was beginning to interact withthe composite fibers after only three weeks. There were no distinctdifferences between the three and six week composite sections asobserved using light microscopy.

The interface between the polymer and bone was sometimes interposed byfibrous tissue, but often had spots of apparent bone contact. There wasno interdigitation between the bone apposed to the polymer as wastypically observed with the composite implants. As for the composites,there were no distinct differences between the three and six weekpolymer sections as observed using light microscopy.

Scanning electron microscopy revealed bone tissue in direct appositionto bioactive glass fibers after six weeks of implantation.Morphologically, it appears as if a fiber in FIG. 11 is beingincorporated into the bony matrix. EDXA indicated that both the fiberarea and the web consisted of calcium and phosphorous. This is mostlikely an example of a fiber which has partially resorbed, allowing thebone to infiltrate the region.

The interface measured between the polymer region of composite materialwhich was implanted for three weeks and bone tissue was approximately3-4 μm thick. Calcium, phosphorous, sulfur, and silicon were detected inthis layer by EDXA. Silicon was not detected on the bone or polymer sideof the interface. This same observation was made on a six week compositespecimen, where the interfacial layer was 4-5μm thick.

The areas where glass fibers were exposed to bone tissue revealed bonetissue adjacent to the glass fibers without an interposing fibroustissue layer. A calcium-phosphate-rich reaction layer was detected onthe surface of glass fibers which were in contact with bone tissue.However, a distinct region of a silica-rich layer was not detectedthrough SEM/EDXA analysis. This may be due to the detection limit of theEDXA corresponding to the thickness of reaction layer to be detected.Although the thickness of the weak silica-gel layer cannot bequantified, it can be deduced that the layer may have been no thickerthan the spatial resolution of the EDXA technique (approximately 2 μm).Previous studies of bioactive glass composite show silica-gel thicknesslayers to be one to two orders of magnitude greater than this (Van Hoveet al., 1993, supra) even at reduced rates of reactions. It has beenhypothesized that a reduction in the thickness of the weak silica-gellayer will lead to increased bond strength between bioactive glass andbone (Van Hove et al., 1993, supra).

The reduced rate of reactivity, resultant thickness of the reactionlayer, resultant increase in apposition of bone, and concomitant bondstrength are all related to the glass composition, more specifically,the Al₂ O₃ content.

Based upon the foregoing, it will be realized that a number ofembodiments of the present invention beyond those discussed in detailabove are possible. Such embodiments, however, will still employ thespirit of the present invention and, accordingly, reference should bemade to the appended claims in order to determine the full scope of thepresent invention.

What is claimed is:
 1. A biocompatible composite of tows of bone bioactive fibers comprising at least 19% Na₂ O by mole and greater than 0.2% Al₂ O₃ by mole, said tows of bioactive fibers intermingled with tows of structural fibers in a nonbioabsorbable polymeric matrix.
 2. The composite of claim 1, wherein the bone bioactive fibers are arranged in a predetermined distribution and a section of a surface of the composite to be affixed to bone is comprised of about 30% or more bone bioactive fibers.
 3. The composite of claim 1 wherein the structural fiber is a carbon fiber.
 4. The composite of claim 1 wherein the polymeric material is chosen from the group consisting of: polysulfone; PEEK; and PEKK.
 5. The composite of claim 1, wherein the bone bioactive fibers comprise 40-60% SiO₂, 19-30% Na₂ O, 10-21% CaO, 0-4% P₂ O₅, and 0.2-1% Al₂ O₃ by mole.
 6. The composite of claim 1, wherein the bone bioactive fibers comprise 45-55% SiO₂, 19-30% Na₂ O, 15-20% CaO, 0-3% P₂ O₅, and 0.2-1% Al₂ O₃ by mole.
 7. The composite of claim 1, further comprising a modifier selected from the group consisting of K₂ O, MgO, and F₂.
 8. The composite of claim 1 wherein the bone bioactive fibers have a diameter of from about 5 to about 25 microns. 